Early goal-directed resuscitation of patients with septic shock: current evidence and future directions.

Severe sepsis and septic shock are among the leading causes of mortality in the intensive care unit. Over a decade ago, early goal-directed therapy (EGDT) emerged as a novel approach for reducing sepsis mortality and was incorporated into guidelines published by the international Surviving Sepsis Campaign. In addition to requiring early detection of sepsis and prompt initiation of antibiotics, the EGDT protocol requires invasive patient monitoring to guide resuscitation with intravenous fluids, vasopressors, red cell transfusions, and inotropes. The effect of these measures on patient outcomes, however, remains controversial. Recently, three large randomized trials were undertaken to re-examine the effect of EGDT on morbidity and mortality: the ProCESS trial in the United States, the ARISE trial in Australia and New Zealand, and the ProMISe trial in England. These trials showed that EGDT did not significantly decrease mortality in patients with septic shock compared with usual care. In particular, whereas early administration of antibiotics appeared to increase survival, tailoring resuscitation to static measurements of central venous pressure and central venous oxygen saturation did not confer survival benefit to most patients. In the following review, we examine these findings as well as other evidence from recent randomized trials of goal-directed resuscitation. We also discuss future areas of research and emerging paradigms in sepsis trials.

Influenza virus resistance to neuraminidase inhibitors: implications for treatment.

Oseltamivir and Zanamivir are the two main Neuraminidase inhibitors used for the treatment of Influenza. Oseltamivir resistance has been identified in non-pandemic influenza viruses, as well as H1N1 pandemic Influenza A viruses. Resistance is associated with increased morbidity, and poorer outcomes in severely immunocompromised hosts. Newer neuraminidase inhibitors, increased vaccination and combination therapy may be alternatives for the treatment of Influenza in this setting.

Surgical site infection surveillance for neurosurgical procedures: a comparison of passive surveillance by surgeons to active surveillance by infection control professionals.

ISSUE: Surveillance methods for surgical site infections (SSIs) range from patient self-report to active surveillance by infection control professionals (ICPs). Surgeon questionnaires surveying SSIs are typically suboptimal due to bias, lack of standardized criteria to diagnose infection, and poor response rate. Although concurrent surveillance of SSIs by ICPs at our medical center documented an incidence of 2.2 SSIs per 100 procedures, the neurosurgeons perceived a much higher rate of SSIs. PROJECT: The neurosurgeons provided a list of patients they had clinically identified with SSIs over a 7 month period. This list was compared with a line listing of SSIs independently identified by ICPs via concurrent surveillance utilizing the Centers for Disease Control and Prevention (CDC) definitions. RESULTS: A total of 766 procedures were performed. Active surveillance by ICPs detected 17 infections (2.2/100 procedures). Of the 14 cases identified by the neurosurgeons, 3 did not meet the CDC definition of a nosocomial infection. The ICPs identified 6 SSIs not documented by the neurosurgeons. Compared to active surveillance by ICPs, the sensitivity and specificity of the neurosurgeon's identification of SSIs was 64% and 99.6%, respectively. The positive predictive value was 78.6% and the negative predictive value was 99.2%. LESSONS LEARNED: An active surveillance program is necessary for accurate identification of SSIs. The primary problem with passive surveillance by surgeons is failure to capture cases; surgeons missed 36% of cases compared to active surveillance by ICPs.

Mandatory public reporting in the USA: an example to follow?

Increasingly states in the USA are enacting laws mandating reporting and disclosure of hospital-acquired infections (HAIs). The rapid development of legislation has occurred in response to increased coverage of HAIs in the mainstream media coupled with active involvement of consumer advocacy organizations. The transformation of healthcare in the USA into a commodity has fostered a strong role for consumer advocacy to which state legislative bodies have shown willingness to respond.

Hospital-acquired Clostridium difficile-associated disease in the intensive care unit setting: epidemiology, clinical course and outcome.

BACKGROUND: Clostridium difficile-associated disease (CDAD) is a serious nosocomial infection, however few studies have assessed CDAD outcome in the intensive care unit (ICU). We evaluated the epidemiology, clinical course and outcome of hospital-acquired CDAD in the critical care setting. METHODS: We performed a historical cohort study on 58 adults with a positive C. difficile cytotoxin assay result occurring in intensive care units. RESULTS: Sixty-two percent of patients had concurrent infections, 50% of which were bloodstream infections. The most frequently prescribed antimicrobials prior to CDAD were anti-anaerobic agents (60.3%). Septic shock occurred in 32.8% of CDAD patients. The in-hospital mortality was 27.6%. Univariate analysis revealed that SOFA score, at least one organ failure and age were predictors of mortality. Charlson score >/=3, gender, concurrent infection, and number of days with diarrhea before a positive C. difficile toxin assay were not significant predictors of mortality on univariate analysis. Independent predictors for death were SOFA score at infection onset (per 1-point increment, OR 1.40; CI95 1.13-1.75) and age (per 1-year increment, OR 1.10; CI95 1.02-1.19). CONCLUSION: In ICU patients with CDAD, advanced age and increased severity of illness at the onset of infection, as measured by the SOFA score, are independent predictors of death.

Systemic inflammatory response syndrome in nosocomial bloodstream infections with Pseudomonas aeruginosa and Enterococcus Species: comparison of elderly and nonelderly patients.

OBJECTIVES: To determine whether the systemic inflammatory response syndrome (SIRS), clinical course, and outcome of monomicrobial nosocomial bloodstream infection (BSI) due to Pseudomonas aeruginosa or Enterococcus spp. is different in elderly patients than in younger patients. DESIGN: Historical cohort study. SETTING: An 820-bed tertiary care facility. PARTICIPANTS: One hundred twenty-seven adults with P. aeruginosa or enterococcal BSI. MEASUREMENTS: SIRS scores were determined 2 days before the first positive blood culture through 14 days afterwards. Elderly patients (> or =65, n=37) were compared with nonelderly patients (<65, n=90). Variables significant for predicting mortality in univariate analysis were entered into a logistic regression model. RESULTS: No difference in SIRS was detected between the two groups. No significant difference was noted in the incidence of organ failure, 7-day mortality, or overall mortality between the two groups. Univariate analysis revealed that Acute Physiology And Chronic Health Evaluation (APACHE) II score of 15 or greater at BSI onset; adjusted APACHE II score (points for age excluded) of 15 or greater at BSI onset; and respiratory, cardiovascular, renal, hematological, and hepatic failure were predictors of mortality. Age, sex, use of empirical antimicrobial therapy, and infection with imipenem-resistant P. aeruginosa or vancomycin-resistant enterococci did not predict mortality. Multivariate analysis revealed that hematological failure (odds ratio (OR)=8.1, 95% confidence interval (CI)=2.78-23.47), cardiovascular failure (OR=4.7, 95% CI=1.69-13.10), and adjusted APACHE II > or = 15 at BSI onset (OR=3.1, 95% CI=1.12-8.81) independently predicted death. CONCLUSION: Elderly patients did not differ from nonelderly patients with respect to severity of illness before or at the time of BSI. Elderly patients with pseudomonal or enterococcal BSIs did not have a greater mortality than nonelderly patients.

Comparison of severity of illness scoring systems for patients with nosocomial bloodstream infection due to Pseudomonas aeruginosa.

BACKGROUND: Several acute illness severity scores have been proposed for evaluating patients on admission to intensive care units but these have not been compared for patients with nosocomial bloodstream infection (nBSI). We compared three severity of illness scoring systems for predicting mortality in patients with nBSI due to Pseudomonas aeruginosa. METHODS: We performed a historical cohort study on 63 adults in intensive care units with P. aeruginosa monomicrobial nBSI. RESULTS: The Acute Physiology, Age, Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Simplified Acute Physiologic Score (SAPS II), were calculated daily from 2 days prior through 2 days after the first positive blood culture. Calculation of the area under the receiver operating characteristic (ROC) curve confirmed that APACHE II and SAPS II at day -1 and SOFA at day +1 were better predictors of outcome than days -2, 0 and day 2 of BSI. By stepwise logistic regression analysis of these three scoring systems, SAPS II (OR: 13.03, CI95% 2.51-70.49) and APACHE II (OR: 12.51, CI95% 3.12-50.09) on day -1 were the best predictors for mortality. CONCLUSION: SAPS II and APACHE II are more accurate than the SOFA score for predicting mortality in this group of patients at day -1 of BSI.

Systemic inflammatory response syndrome in adult patients with nosocomial bloodstream infections due to enterococci.

BACKGROUND: Enterococci are the third leading cause of nosocomial bloodstream infection (BSI). Vancomycin resistant enterococci are common and provide treatment challenges; however questions remain about VRE's pathogenicity and its direct clinical impact. This study analyzed the inflammatory response of Enterococcal BSI, contrasting infections from vancomycin-resistant and vancomycin-susceptible isolates. METHODS: We performed a historical cohort study on 50 adults with enterococcal BSI to evaluate the associated systemic inflammatory response syndrome (SIRS) and mortality. We examined SIRS scores 2 days prior through 14 days after the first positive blood culture. Vancomycin resistant (n = 17) and susceptible infections (n = 33) were compared. Variables significant in univariate analysis were entered into a logistic regression model to determine the affect on mortality. RESULTS: 60% of BSI were caused by E. faecalis and 34% by E. faecium. 34% of the isolates were vancomycin resistant. Mean APACHE II (A2) score on the day of BSI was 16. Appropriate antimicrobials were begun within 24 hours in 52%. Septic shock occurred in 62% and severe sepsis in an additional 18%. Incidence of organ failure was as follows: respiratory 42%, renal 48%, hematologic 44%, hepatic 26%. Crude mortality was 48%. Progression to septic shock was associated with death (OR 14.9, p < .001). There was no difference in A2 scores on days -2, -1 and 0 between the VRE and VSE groups. Maximal SIR (severe sepsis, septic shock or death) was seen on day 2 for VSE BSI vs. day 8 for VRE. No significant difference was noted in the incidence of organ failure, 7-day or overall mortality between the two groups. Univariate analysis revealed that AP2>18 at BSI onset, and respiratory, cardiovascular, renal, hematologic and hepatic failure were associated with death, but time to appropriate therapy >24 hours, age, and infection due to VRE were not. Multivariate analysis revealed that hematologic (OR 8.4, p = .025) and cardiovascular failure (OR 7.5, p = 032) independently predicted death. CONCLUSION: In patients with enterococcal BSI, (1) the incidence of septic shock and organ failure is high, (2) patients with VRE BSI are not more acutely ill prior to infection than those with VSE BSI, and (3) the development of hematologic or cardiovascular failure independently predicts death.

Acid suppressive therapy and the effects on protease inhibitors.

OBJECTIVE: To review the literature associated with the pharmacokinetic interaction between protease inhibitors (PIs) and acid suppressive therapies and to characterize the impact of this interaction on virologic and immunologic outcomes. DATA SOURCES: A MEDLINE search (1966-October 2006) was conducted using the names of the 10 PIs and specific acid suppressive therapies including antacids, histamine(2)-receptor antagonists, and proton pump inhibitors. Abstracts and poster presentations from recent HIV/AIDS meetings were reviewed for relevance. References from retrieved articles, as well as product packaging and manufacturer information, were evaluated. STUDY SELECTION AND DATA EXTRACTION: Pertinent pharmacokinetic, immunologic, and virologic studies, in healthy and HIV-infected patients, evaluating the use of a PI and acid suppressive therapy were reviewed. DATA SYNTHESIS: Potential interactions between concomitant acid suppressive therapy and PIs were evaluated. Available information indicates that indinavir and atazanavir require an acidic gastric medium for adequate absorption. Indinavir pharmacokinetic parameters are variable with acid suppressive therapy but primarily result in decreased oral absorption. This interaction abates with concurrent ritonavir use. No immunologic or virologic data are available regarding the concomitant use of indinavir and acid suppressive therapy. The minimum concentration of atazanavir, area under the concentration-time curve, and maximum concentration are significantly reduced when used concurrently with acid suppressive therapy. Atazanavir 300 or 400 mg boosted with ritonavir 100 mg increases plasma concentrations when used with acid suppressive drugs. Virologic and immunologic outcomes appear stable when boosted atazanavir is used in HIV-positive patients. Atazanavir therapeutic monitoring should be considered when used in combination with acid suppressive therapy. CONCLUSIONS: Of the PIs reviewed, significant pharmacokinetic interactions exist between acid suppressive therapy and indinavir or atazanavir. These PIs should be used with low-dose ritonavir if acid suppressive therapy is necessary.

A statewide survey of nosocomial infection surveillance in acute care hospitals.

Increasingly, states are considering mandating the reporting of nosocomial infection data. To determine the impact of potential legislation, a questionnaire was mailed to the infection control department of each hospital in Virginia to assess the size of the infection control workforce and methodologies used for nosocomial infection surveillance. Most hospitals (64%) had 1 ICP full-time equivalent (FTE), and, at 86% of hospitals, the ICPs had other major responsibilities. The estimated mean additional ICP FTE required to perform hospital-wide surveillance was 1.7. Statewide, an additional 160 ICPs at an estimated annual cost of 11.5 million dollars would be required if reporting of all nosocomial infections were mandated.

Bacteremias: a leading cause of death.

Bloodstream infections (BSIs), recognized to be a major cause of morbidity and mortality globally, are increasing in incidence. The reported rates of crude and attributable mortality vary, possibly due to heterogeneity in patient populations and methodology. Few studies, however, have focused on pathogen-specific attributable mortality. These studies include S. aureus, coagulase-negative staphylococci and enterococcus. Other studies of attributable mortality have been conducted in select populations such as nosocomial and community-acquired cohorts, intensive care units, neutropenic patients, and HIV-positive patients. Regrettably, despite advances in treatment and intensive care facilities, mortality remains high.

Comparison of the systemic inflammatory response syndrome between monomicrobial and polymicrobial Pseudomonas aeruginosa nosocomial bloodstream infections.

BACKGROUND: Some studies of nosocomial bloodstream infection (nBSI) have demonstrated a higher mortality for polymicrobial bacteremia when compared to monomicrobial nBSI. The purpose of this study was to compare differences in systemic inflammatory response and mortality between monomicrobial and polymicrobial nBSI with Pseudomonas aeruginosa. METHODS: We performed a historical cohort study on 98 adults with P. aeruginosa (Pa) nBSI. SIRS scores were determined 2 days prior to the first positive blood culture through 14 days afterwards. Monomicrobial (n = 77) and polymicrobial BSIs (n = 21) were compared. RESULTS: 78.6% of BSIs were caused by monomicrobial P. aeruginosa infection (MPa) and 21.4% by polymicrobial P. aeruginosa infection (PPa). Median APACHE II score on the day of BSI was 22 for MPa and 23 for PPa BSIs. Septic shock occurred in 33.3% of PPa and in 39.0% of MPa (p = 0.64). Progression to septic shock was associated with death more frequently in PPa (OR 38.5, CI95 2.9-508.5) than MPa (OR 4.5, CI95 1.7-12.1). Maximal SIR (severe sepsis, septic shock or death) was seen on day 0 for PPa BSI vs. day 1 for MPa. No significant difference was noted in the incidence of organ failure, 7-day or overall mortality between the two groups. Univariate analysis revealed that APACHE II score > or = 20 at BSI onset, Charlson weighted comorbidity index > or = 3, burn injury and respiratory, cardiovascular, renal and hematologic failure were associated with death, while age, malignant disease, diabetes mellitus, hepatic failure, gastrointestinal complications, inappropriate antimicrobial therapy, infection with imipenem resistant P. aeruginosa and polymicrobial nBSI were not. Multivariate analysis revealed that hematologic failure (p < 0.001) and APACHE II score > or = 20 at BSI onset (p = 0.005) independently predicted death. CONCLUSION: In this historical cohort study of nBSI with P. aeruginosa, the incidence of septic shock and organ failure was high in both groups. Additionally, patients with PPa BSI were not more acutely ill, as judged by APACHE II score prior to blood culture positivity than those with MPa BSI. Using multivariable logistic regression analysis, the development of hematologic failure and APACHE II score > or = 20 at BSI onset were independent predictors of death; however, PPa BSI was not.

Antibiotics for anthrax: patient requests and physician prescribing practices during the 2001 New York City attacks.

BACKGROUND: Little is known about patient encounters with primary care physicians and prescribing practices during the 2001 US anthrax attacks. METHODS: We retrospectively reviewed the electronic medical record of outpatient telephone and clinic visits at a large primary care practice in New York City from September 11 to December 31, 2001, to identify physician- and patient-related factors that were associated with prescribing antibiotics for anthrax prophylaxis. RESULTS: Average daily patient volume from October to December was higher in 2001 (221.2 patients per day) compared with 2000 (199.1; P<.01) and 2002 (215.8; P = .14). Patient-initiated discussion about anthrax or smallpox were involved in 244 patient contacts with 63 physicians, including 92 (0.6%) of 14917 telephone contacts and 152 (1.0%) of 15 539 office visits. Fifty patients (21%) requested antibiotics or vaccines and 52 (22%) received antibiotics: 39 received ciprofloxacin; 12, doxycycline; and 1, both drugs. Independent predictors of receiving anthrax prophylaxis included requesting medication (odds ratio [OR], 8.1; 95% confidence interval [CI], 3.5-18.6), reporting powder or workplace exposure (OR, 4.5; 95% CI, 2.1-10.0), having an abnormal physical examination finding (OR, 3.9; 95% CI, 1.4-11.0), and being asymptomatic (reporting any illness symptoms was associated with an OR of 0.3 [95% CI, 0.1-0.6]). CONCLUSIONS: Primary care physicians played an important and heretofore underdocumented role in responding to the 2001 anthrax attacks. Prescription of prophylactic antibiotics for anthrax was uncommon and appears to have been selective among concerned patients. These results highlight the importance of including primary care physicians in community-wide bioterrorism response planning.

Accuracy of screening for inhalational anthrax after a bioterrorist attack.

BACKGROUND: Bioterrorism using anthrax claimed five lives in the United States in 2001 and remains a potential public health threat. In the aftermath of a large-scale anthrax attack, mass screening to identify early inhalational anthrax may improve both the management of individual cases and the efficiency of health resource utilization. PURPOSE: To develop the evidence base for outpatient anthrax screening protocols by quantifying differences in clinical presentation between inhalational anthrax and common viral respiratory tract infections. DESIGN: Review, compilation, and data extraction from English-language case reports of inhalational anthrax and epidemiologic studies of influenza and other viral respiratory infections. DATA SOURCES: 13 reports of 28 cases of inhalational anthrax from 1920 to 2001 and 5 studies reporting on the clinical features of 2762 cases of influenza and 1932 cases of noninfluenza viral respiratory disease. DATA SYNTHESIS: Characterization of presenting clinical symptoms in anthrax and viral disease and calculation of likelihood ratios for the presence of selected clinical features. RESULTS: Fever and cough do not reliably discriminate between inhalational anthrax and viral respiratory tract infection. Features suggestive of anthrax include the presence of nonheadache neurologic symptoms (positive likelihood ratio cannot be calculated), dyspnea (positive likelihood ratio, 5.3 [95% CI, 3.7 to 7.4]), nausea or vomiting (positive likelihood ratio, 5.1 [CI, 3.0 to 8.5]), and finding of any abnormality on lung auscultation (positive likelihood ratio, 8.1 [CI, 5.3 to 12.5]). In contrast, rhinorrhea (positive likelihood ratio, 0.2 [CI, 0.1 to 0.4]) and sore throat (positive likelihood ratio, 0.2 [CI, 0.1 to 0.5]) are more suggestive of viral respiratory tract infection. CONCLUSION: Inhalational anthrax has characteristic clinical features that are distinct from those seen in common viral respiratory tract infections. Screening protocols based on these features may improve rapid identification of patients with presumptive inhalational anthrax in the setting of a large-scale anthrax attack.

Use of intravenous immunoglobulin in critically ill patients.

Intravenous immunoglobulin (IVIG) has been suggested for the treatment of many ailments due to its ability to modulate the immune system and to provide passive immunity to commonly circulating pathogens. Its use as primary and adjunctive therapy for the treatment of conditions affecting critically ill patients is an attractive option, especially when alternative therapy does not exist. The body of literature on the use of IVIG for the treatment of several serious conditions, including sepsis, toxic shock syndrome, acute myocarditis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and H1N1 influenza, were reviewed. Despite advances in treatment of these conditions since they were first described, there remains a paucity of well-designed studies on the use of IVIG for their treatment. Therefore, the use of IVIG for treatment of these conditions remains controversial.

Access and Barriers to Healthcare Vary among Three Neighboring Communities in Northern Honduras.

Objective. The aim of this study is to describe and compare access and barriers to health services in three proximal yet topographically distinct communities in northern Honduras served by the nonprofit organization the Honduras Outreach Medical Brigada Relief Effort (HOMBRE). Methods. Study personnel employed a 25-item questionnaire in Spanish at the point of care during HOMBRE clinics in Coyoles, Lomitas, and La Hicaca (N = 220). We describe and compare the responses between sites, using Chi-squared and Fisher Exact tests. Results. Respondents in Lomitas demonstrated the greatest limitations in access and greatest barriers to care of all sites. Major limitations in access included "never" being able to obtain a blood test, obtain radiology services, and see a specialist. Major barriers were cost, distance, facility overcrowding, transportation, being too ill to go, inability to take time off work, and lack of alternate childcare. Conclusions. Despite being under the same local health authority, geographically remote Honduran communities experience greater burdens in healthcare access and barriers than neighboring communities of the same region.

A crossover trial of antimicrobial scrubs to reduce methicillin-resistant Staphylococcus aureus burden on healthcare worker apparel.

BACKGROUND: The impact of antimicrobial scrubs on healthcare worker (HCW) bacterial burden is unknown. Objective. To determine the effectiveness of antimicrobial scrubs on hand and apparel bacterial burden. DESIGN: Prospective, crossover trial. SETTING AND PARTICIPANTS: Thirty HCWs randomized to study versus control scrubs in an intensive care unit. METHODS: Weekly microbiology samples were obtained from scrub abdominal area, cargo pocket, and hands. Mean log colony-forming unit (CFU) counts were calculated. Compliance with hand hygiene practices was measured. Apparel and hand mean log CFU counts were compared. RESULTS: Adherence measures were 78% (910/1,173) for hand hygiene and 82% (223/273) for scrubs. Culture compliance was 67% (306/460). No differences were observed in bacterial hand burden or in HCWs with unique positive scrub cultures. No difference in vancomycin-resistant enterococci (VRE) and gram-negative rod (GNR) burden was observed. A difference in mean log methicillin-resistant Staphylococcus aureus (MRSA) CFU count was found between study and control scrubs for leg cargo pocket (mean log CFUs, 11.84 control scrub vs 6.71 study scrub; [Formula: see text]), abdominal area (mean log CFUs, 11.35 control scrub vs 7.54 study scrub; [Formula: see text]), leg cargo pocket at the beginning of shift (mean log CFUs, 11.96 control scrub vs 4.87 study scrub; [Formula: see text]), and abdominal area pocket at the end of shift (mean log CFUs, 12.14 control scrubs vs 8.22 study scrub; [Formula: see text]). CONCLUSIONS: Study scrubs were associated with a 4-7 mean log reduction in MRSA burden but not VRE or GNRs. A prospective trial is needed to measure the impact of antimicrobial impregnated apparel on MRSA transmission rates.

Treatment of severe cases of pandemic (H1N1) 2009 influenza: review of antivirals and adjuvant therapy.

Three worldwide influenza pandemics were reported in the 20th century: in 1918, 1957 and 1968. All three pandemics were caused by different sub-types of Influenza A viruses: H1N1, H2N2 and H3N2 respectively. In early March 2009, the first cases of influenza -like illness (ILI) were reported from Mexico. This strain was identified as influenza A/ H1N1 strain. Pandemic (H1N1) 2009 influenza most commonly causes a self-limited illness, however, significant morbidity and mortality were reported in the young, the obese and in pregnant women. The drugs of choice for treatment and prophylaxis of pandemic (H1N1) 2009 influenza are the neuraminidase inhibitors, Oseltamivir and Zanamivir. While a few cases of Oseltamivir-resistance are reported, these isolates still retained their susceptibility to the inhaled Neuraminidase inhibitor, Zanamivir. Pandemic (H1N1) 2009 influenza virus is routinely resistant to the adamantanes: Amantadine and Rimantadine. These agents should not be used for the treatment or prophylaxis of pandemic (H1N1) 2009 influenza. The FDA recently approved the emergency use of Peramivir, an intravenous neuraminidase inhibitor, for the treatment of patients with severe influenza. We discuss the use of available antivirals, as well as the effectiveness of adjunctive therapies with immunomodulatory and anti-inflammatory agents, such as immunoglobulins and statins, for the treatment and management of patients with severe H1N1 influenza. This review summarizes the recent patents for the use of antivirals in treatment of severe influenza.